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Updated: Nov 2, 2025
A Seminiferous Tubule Squash Technique for the Cytological Analysis of Spermatogenesis Using the Mouse Model
Published on: February 6, 2018
Hypomorphic and hypermorphic mouse models of Fsip2 indicate its dosage-dependent roles in sperm tail and acrosome
Xiang Fang1, Yaser Gamallat1, Zhiheng Chen2
1Laboratory of Medical Systems Biology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, 510623 Guangzhou, China.
Abstract:
Loss-of-function mutations in multiple morphological abnormalities of the sperm flagella (MMAF)-associated genes lead to decreased sperm motility and impaired male fertility. As an MMAF gene, the function of fibrous sheath-interacting protein 2 (FSIP2) remains largely unknown. In this work, we identified a homozygous truncating mutation of FSIP2 in an infertile patient. Accordingly, we constructed a knock-in (KI) mouse model with this mutation. In parallel, we established an Fsip2 overexpression (OE) mouse model. Remarkably, KI mice presented with the typical MMAF phenotype, whereas OE mice showed no gross anomaly except for sperm tails with increased length. Single-cell RNA sequencing of the testes uncovered altered expression of genes related to sperm flagellum, acrosomal vesicle and spermatid development. We confirmed the expression of Fsip2 at the acrosome and the physical interaction of this gene with Acrv1, an acrosomal marker. Proteomic analysis of the testes revealed changes in proteins sited at the fibrous sheath, mitochondrial sheath and acrosomal vesicle. We also pinpointed the crucial motifs of Fsip2 that are evolutionarily conserved in species with internal fertilization. Thus, this work reveals the dosage-dependent roles of Fsip2 in sperm tail and acrosome formation.
Insights
Loss-of-function mutations in fibrous sheath-interacting protein 2 (FSIP2) cause male infertility. This study reveals FSIP2
Area of Science:
- Reproductive Biology
- Genetics
- Molecular Biology
Background:
- Multiple Morphological Abnormalities of the Sperm Flagella (MMAF) genes are crucial for male fertility.
- The specific function of Fibrous Sheath Interacting Protein 2 (FSIP2), an MMAF-associated gene, is largely uncharacterized.
Purpose of the Study:
- To investigate the function of FSIP2 in sperm formation and male fertility.
- To elucidate the role of FSIP2 mutations and altered expression levels in reproductive health.
Main Methods:
- Identification of a homozygous FSIP2 mutation in an infertile patient.
- Generation of FSIP2 knock-in (KI) and overexpression (OE) mouse models.
- Single-cell RNA sequencing, proteomics, and analysis of conserved motifs.
Main Results:
- KI mice exhibited the MMAF phenotype with impaired sperm motility.
- OE mice showed elongated sperm tails but no other gross anomalies.
- FSIP2 interacts with the acrosomal marker Acrv1, and its dosage affects sperm tail and acrosome formation.
Conclusions:
- FSIP2 plays a dosage-dependent role in sperm tail and acrosome development.
- FSIP2 mutations can lead to male infertility.
- This study provides insights into the molecular mechanisms underlying sperm flagellum and acrosome formation.
